Polyglycolic acid is a polyester formed by dehydration-polycondensation of glycolic acid (i.e., α-hydroxylacetic acid) and having the following formula:

Polyglycolic acid is a biodegradable polymer that is hydrolyzed in vivo and, in natural environments, is metabolized and decomposed by microorganisms into water and carbonic acid gas. For this reason, the polyglycolic acid now attracts attention as environment-friendly polymer substitutes for medical materials or general-purpose. However, it is still difficult to obtain any polyglycolic acid having a high molecular weight by means of the dehydration-polycondensation of glycolic acid.
According to another polyglycolic acid production process so far known in the art, glycolide of the following formula, which is a cyclic dimer ester of glycolic acid is first synthesized.

Then, this glycolide is subjected to ring-opening polymerization in the presence of a catalyst such as stannous octoate.
To produce polyglycolic acid (also called “polyglycolide”) having a high molecular weight by the ring-opening polymerization of glycolide, it is required to use high-purity polyglycolide as the starting material. To use glycolide as the starting material to produce polyglycolic acid on an industrial scale, it is thus essential to economically feed such high-purity glycolide.
Glycolide is a cyclic ester compound having the structure wherein two water molecules are eliminated from two glyclolic acid molecules. Only by the esterification reaction of glycolic acid, however, any glycolide cannot be obtained because of the formation of glycolic acid oligomers. So far, various glycolide production processes have been proposed.
U.S. Pat. No. 2,668,162 discloses a process in which a glycolic acid oligomer is crushed into powders and heated at 270 to 285° C. under an ultra-high vacuum (12 to 15 Torr (1.6 to 2.0 kPa)) while the powders are fed to a reaction vessel in small portions (about 20 g/hour) for depolymerization, and the resultant glycolide-containing vapor is entrapped. This process, albeit being suitable for small-scale production, is found to have difficulty in large-scale production and so unsuitable for mass production. In addition, this process causes the oligomer to become heavy upon heating and so remain in the form of much residues in the reaction vessel, resulting in decreased glycolide yields and the need of cleaning off the residues. To add to this, the process makes glycolide (having a melting point of 82 to 83° C.) and byproducts likely to separate out in recovery lines, ending up with troubles such as line clogging.
U.S. Pat. No. 4,727,163 shows a glycolide production process wherein a polyether having good thermal stability is used as a substrate, a small amount of glycolic acid is then block copolymerized with the substrate to obtain a block copolymer, and the block copolymer is finally heated for depolymerization. However, this block copolymerization process is intractable and incurs some considerable production cost. In addition, the process makes glycolide and byproducts likely to separate out in recovery lines, leading to troubles such as line clogging.
U.S. Pat. Nos. 4,835,293 and 5,023,349 teach a process wherein an α-hydroxycarboxylic acid oligomer such as a polyglycolic acid oligomer is heated into a melt, and a cyclic dimer esters such as glycolide generated and vaporized out of the surface of the melt is entrained in an inert gas such as nitrogen gas and stripped in a low-boiling solvent such as acetone or ethyl acetate for recovery. With this process, it is still difficult to cut back on production costs, because of problems such as a slow formation rate of the cyclic dimer ester, possible formation of heavy materials in the melt, and the need for preheating for blowing a large amount of inert gas into the melt.
French Patent No. 2692263-A1 discloses a process for the production of a cyclic dimer ester wherein an oligomer of an α-hydroxycarboxylic acid or its ester or salt is added to a solvent with a catalyst added thereto, and then stirred in the presence of heat for catalytic decomposition. This process is carried out under normal or applied pressure, using a solvent suitable for entraining the cyclic dimer ester therein in a gaseous phase state. The gaseous phase is then condensed for the recovery of the cyclic dimer ester and solvent. The specification refers to only an example wherein a lactic acid oligomer is used as the raw feed and dodecane (having a boiling point of about 214° C.) is employed as the solvent. However, the results of follow-up experimentation made by the inventors under the same conditions as described in the example and using a glycolic acid oligomer and dodecane showed that heavy materials begin to form simultaneously with the start of the depolymerization reaction, the formation of glycolide stops at a point of time when a very slight amount of glycolide is formed, and much labor is needed for cleaning reaction residues because they are too viscous.
JP-A 09-328481 filed by the applicant of this application discloses a process comprising the steps of heating and depolymerizing an α-hydroxycarboxylic acid oligomer such as a glycolic acid oligomer in a polar organic solvent having a high boiling point, and distilling out the resultant cyclic dimer ester such as glycolide together with the polar organic solvent, and removing the cyclic dimer ester from the distillates.
The results of the inventors' subsequent investigation have showed that if a polyalkylene glycol ether having satisfactory thermal stability is used as the polar organic solvent in this process, cost reductions can then be achieved by recycling the solvent.
When a glycolic acid oligomer synthesized with a commercially available industrial-grade aqueous solution of glycolic acid is depolymerized in a high-boiling polar organic solvent, however, it has been found that the depolymerization reaction system becomes gradually unstable and so the formation rate of glycolide becomes low. To achieve efficient mass-production of glycolide by the aforesaid process, the depolymerization reaction should preferably be carried out continuously or repeatedly in the same reaction vessel.
That is, the depolymerization reaction system comprising a glycolic acid oligomer and a polar organic solvent is heated to depolymerize the glycolic acid oligomer into glycolide, and the resulting glycolide is distilled together with the polar organic solvent out of the depolymerization reaction system. It is here noted that if the solution remaining in the depolymerization reaction system is continuously or intermittently replenished with a fresh glycolic acid oligomer and a fresh polar organic solvent, it is then possible to carry out the depolymerization reaction continuously or repeatedly over an extended period.
As the depolymerization reaction takes place continuously or repeatedly within the same reaction vessel, however, the formation rate of glycolide decreases gradually, and the depolymerization reaction system becomes viscous with a buildup of heavier materials, resulting in a possibility that the system may boil suddenly. To be more specific, when the depolymerization reaction is repeated at least ten times within the same reaction vessel, it is found that there is a noticeable drop of the distillation rate of glycolide.
The inventors have made further studies to elucidate the cause of this problem. As a result of hydrolysis under alkaline conditions of a glycolic acid oligomer synthesized using a commercially available industrial-grade aqueous solution of glycolic acid, it has thus been found that such a glycolic acid oligomer contains, in addition to glycolic acid, organic acids such as diglycolic acid and methoxy acetic acid. Although depending on how to produce glycolic acid, oxalic acid may also be detected.
When the depolymerization reaction is carried out continuously or repeatedly while this system Is replenished with a fresh glycolic acid oligomer and a fresh polar organic solvent, these organic acids are built up in the depolymerization reaction system because of their relatively high boiling points. The accumulation of the organic acids within the depolymerization reaction system has now been found to have adverse influences on the depolymerization reaction.
The instability of the depolymerization reaction system and the decreased formation rate of glycolide due to such organic acid impurities may possibly be prevented by using an aqueous solution of high-purity glycolic acid or purifying an industrial-grade aqueous solution of glycolic acid thereby reducing the organic acid impurity content thereof. However, the glycolic acid purification step costs much, and so goes against glycolide production cost reductions and eventually provides an obstacle to versatile applications of polyglycolic acid.
In addition, even with a glycolic acid oligomer synthesized using an aqueous solution of high-purity glycolic acid or a purified aqueous solution of glycolic acid, the accumulation of slight amounts of organic acid impurities causes the depolymerization reaction to become gradually instable and the formation rate of glycolide to decrease, when the depolymerization reaction is carried out continuously or repetitively over an extended period. Thus, further improvements are still needed so as to achieve stable, efficient, low-cost production of high-purity glycolide on an industrial scale.